With the development of pharmaceutical science, therapeutic advantages of oral sustained-release preparations over ordinary immediate-release preparations have been recognized. The sustained-release preparation has longer drug release time, and more stable drug release, so that the fluctuation in plasma drug concentration is reduced in patients, which can reduce the times of medication and improve therapeutic effects, while also reduce the occurrence of side effects. Therefore, in the research & development of pharmaceutical preparations, more and more drugs are designed as sustained-release preparations.
In practical applications, in order to achieve the purpose of controlling drug release, it is often necessary to use more adjuvant materials that control drug release. However, the use of a large amount of adjuvant materials inevitably leads to a larger weight and volume of the final preparations, thereby causing difficulties for patients to swallow.
According to statistical data from the Food and Drug Administration, 16 million people in the United States have difficulties in swallowing. Among them, 8% have experienced cases where the preparation is too large to be swallowed and the medication is not strictly taken as prescribed, even 4% give up the treatment with a certain preparation as it is unable to be swallowed. Therefore, it is a subject closely related to therapeutic effects of a drug in terms of controlling the weight and volume of a pharmaceutical preparation to make it easy for patients to swallow.
For example, metformin hydrochloride framework sustained-released tablets have two commonly used specifications of 500 mg and 1000 mg. A framework controlled-release mechanism is used by the metformin hydrochloride sustained-released tablets sold at the pharmaceutical market in China to control drug release, and a framework sustained-released tablet with a specification of 500 mg has a weight of more than 1 gram (about 1.1 grams). For convenience of administration by patient, tablets are made into capsule-shaped ones to reduce their cross-sectional area through the esophagus when swallowing. If a framework sustained-released tablet with a specification of 1000 mg is produced by way of framework sustained-release method, the weight will reach more than 2 g. Even if the capsule-shaped design is used, the volume is too large, which will make it difficult for patient to swallow. Therefore, the metformin hydrochloride sustained-released tablets sold at the pharmaceutical market in China only have a maximum specification of 500 mg, rather than a specification of 1000 mg.
Among metformin hydrochloride controlled-release preparations sold at the American market, there are metformin hydrochloride osmotic pump tablets with a specification of 1000 mg (trade name: FORTMET) manufactured by Andrx Labs. Since in an osmotic pump preparation, a coating film is used as controlled-release means, a controlled-release effect can be achieved with less adjuvant materials, so that the total weight of such preparation is only about 1.2 grams, which is much lower than the weight of the framework sustained-released tablet (more than 2 grams). A circular-shaped punch is adopted for the FORTMET osmotic pump tablet to press a tablet core, and the punch used for preparing the osmotic pump tablet is a circular-shaped punch for the reason that the tablet core pressed via a circular-shaped punch is isotropic, the tumbling of the tablet core in the coating pan is random in the process of coating, and the probability of receiving the coating liquid in each direction is the same, therefore, the coating film on the entire surface of the tablet is relatively uniform, so that the coating film has good integrity and is not easily broken to cause burst release. However, a circular-shaped punch with a diameter of 13-14 mm is adopted for the FORTMET osmotic pump tablet to press the tablet core, although the weight of the tablet is significantly lower than that of the framework sustained-released tablet, the cross-sectional area is still large and it is still inconvenient to be swallowed.